Cells: The Living Units

Transcription

1 Overview of the Cellular Basis of Life (pp. 62 6) The Plasma Membrane: Structure (pp. 6 67) The Fluid Mosaic Model (pp. 6 66) Membrane Junctions (pp ) The Plasma Membrane: Membrane Transport (pp ) Passive Processes (pp ) Active Processes (pp ) The Plasma Membrane: Generation of a Resting Membrane Potential (pp ) The Plasma Membrane: Cell- Environment Interactions (pp ) Roles of Cell Adhesion Molecules (pp ) Roles of Membrane Receptors (p. 81) Role of Voltage-Sensitive Membrane Channel Proteins (p. 81) The Cytoplasm (pp ) Cytoplasmic Organelles (pp. 8 89) Cellular Extensions (pp ) The Nucleus (pp ) The Nuclear Envelope (pp. 91 9) Nucleoli (p. 9) Chromatin (pp. 9 95) Cell Growth and Reproduction (pp ) The Cell Life Cycle (pp ) Protein Synthesis (pp ) Other Roles of DNA (pp ) Cells: The Living Units Just as bricks and timbers are the structural units of a house, cells are the structural units of all living things, from one-celled generalists like amoebas to complex multicellular organisms such as humans, dogs, and trees. The human body has 50 to 100 trillion of these tiny building blocks. This chapter focuses on structures and functions shared by all cells. We address specialized cells and their unique functions in later chapters. Cytosolic Protein Degradation (pp ) Extracellular Materials (p. 107) Developmental Aspects of Cells (pp ) 61

2 62 UNIT 1 Organization of the Body Overview of the Cellular Basis of Life Define cell. List the three major regions of a generalized cell and indicate the function of each. Fibroblasts Erythrocytes The English scientist Robert Hooke first observed plant cells with a crude microscope in the late 1600s. However, it was not until the 180s that two German scientists, Matthias Schleiden and Theodor Schwann, were bold enough to insist that all living things are composed of cells. The German pathologist Rudolf Virchow extended this idea by contending that cells arise only from other cells. Virchow s proclamation was revolutionary because it openly challenged the widely accepted theory of spontaneous generation, which held that organisms arise spontaneously from garbage or other nonliving matter. Since the late 1800s, cell research has been exceptionally fruitful and provided us with four concepts collectively known as the cell theory: 1. A cell is the basic structural and functional unit of living organisms. So when you define cell properties you are in fact defining the properties of life. 2. The activity of an organism depends on both the individual and the collective activities of its cells.. According to the principle of complementarity of structure and function, the biochemical activities of cells are dictated by the relative number of their specific subcellular structures. 4. Continuity of life from one generation to another has a cellular basis. We will expand on all of these concepts as we progress. Let us begin with the idea that the cell is the smallest living unit. Whatever its form, however it behaves, the cell is the microscopic package that contains all the parts necessary to survive in an ever-changing world. It follows then that loss of cellular homeostasis underlies virtually every disease. The trillions of cells in the human body include over 200 different cell types that vary greatly in shape, size, and function (Figure.1). The spherical fat cells, disc-shaped red blood cells, branching nerve cells, and cubelike cells of kidney tubules are just a few examples of the shapes cells take. Depending on type, cells also vary greatly in length ranging from 2 micrometers (1/12,000 of an inch) in the smallest cells to over a meter in the nerve cells that cause you to wiggle your toes. A cell s shape reflects its function. For example, the flat, tilelike epithelial cells that line the inside of your cheek fit closely together, forming a living barrier that protects underlying tissues from bacterial invasion. Regardless of type, all cells are composed chiefly of carbon, hydrogen, nitrogen, oxygen, and trace amounts of several other elements. In addition, all cells have the same basic parts and some common functions. For this reason, it is possible to speak of a generalized,or composite, cell (Figure.2). Human cells have three main parts: the plasma membrane, the cytoplasm, and the nucleus. The plasma membrane, a fragile Epithelial cells (a) Cells that connect body parts, form linings, or transport gases Skeletal muscle cell (b) Cells that move organs and body parts Fat cell (c) Cell that stores nutrients Nerve cell Macrophage (d) Cell that fights disease (e) Cell that gathers information and controls body functions (f) Cell of reproduction Sperm Smooth muscle cells Figure.1 Cell diversity. (Note that cells are not drawn to the same scale.) barrier, is the outer boundary of the cell. Internal to this membrane is the cytoplasm (si to-plazm), the intracellular fluid that is packed with organelles, small structures that perform specific cell functions. The nucleus (nu kle-us) controls cellular activities and typically it lies near the cell s center. We use these three main parts of the cell to organize the summary in Table. (pp ), and we describe them in greater detail next.

3 Chapter Cells: The Living Units 6 Chromatin Nuclear envelope Nucleolus Nucleus Smooth endoplasmic reticulum Plasma membrane Cytosol Mitochondrion Lysosome Centrioles Centrosome matrix Rough endoplasmic reticulum Ribosomes Golgi apparatus Secretion being released from cell by exocytosis Cytoskeletal elements Microtubule Intermediate filaments Peroxisome Figure.2 Structure of the generalized cell. No cell is exactly like this one, but this composite illustrates features common to many human cells. Note that not all of the organelles are drawn to the same scale in this illustration. CHECK YOUR UNDERSTANDING 1. Name the three basic parts of a cell and describe the function of each. 2. How would you explain the meaning of a generalized cell to a classmate? For answers, see Appendix G. The Plasma Membrane: Structure Describe the chemical composition of the plasma membrane and relate it to membrane functions. Compare the structure and function of tight junctions, desmosomes, and gap junctions. The flexible plasma membrane defines the extent of a cell, thereby separating two of the body s major fluid compartments the intracellular fluid within cells and the extracellular fluid outside cells. The term cell membrane is commonly used as a synonym for plasma membrane, but because nearly all cellular organelles are enclosed in a membrane, in this book we will always refer to the cell s surface, or outer limiting membrane, as the plasma membrane. The plasma membrane is much more than a passive envelope. As you will see, its unique structure allows it to play a dynamic role in many cellular activities. The Fluid Mosaic Model The fluid mosaic model of membrane structure depicts the plasma membrane as an exceedingly thin (7 10 nm) structure

4 64 UNIT 1 Organization of the Body composed of a double layer, or bilayer, of lipid molecules with protein molecules plugged into or dispersed in it (Figure.). The proteins, many of which float in the fluid lipid bilayer,form a constantly changing mosaic pattern. The model is named for this characteristic. Membrane Lipids The lipid bilayer forms the basic fabric of the membrane. It is constructed largely of phospholipids, with smaller amounts of cholesterol and glycolipids. Each lollipop-shaped phospholipid molecule has a polar head that is charged and is hydrophilic (hydro water, philic loving), and an uncharged, nonpolar tail that is made of two fatty acid chains and is hydrophobic (phobia fear). The polar heads are attracted to water the main constituent of both the intracellular and extracellular fluids and so they lie on both the inner and outer surfaces of the membrane. The nonpolar tails, being hydrophobic, avoid water and line up in the center of the membrane. The result is that all biological membranes share a common sandwich-like structure: They are composed of two parallel sheets of phospholipid molecules lying tail to tail, with their polar heads exposed to water both inside and outside the cell. This self-orienting property of phospholipids encourages biological membranes to self-assemble into closed, generally spherical, structures and to reseal themselves quickly when torn. The plasma membrane is a dynamic fluid structure that is in constant flux. Its consistency is like that of olive oil. The lipid molecules of the bilayer move freely from side to side, parallel to the membrane surface, but their polar-nonpolar interactions prevent them from flip-flopping or moving from one phospholipid layer (half of the bilayer) to the other. The inward-facing and outward-facing surfaces of the plasma membrane differ in the kinds and amounts of lipids they contain, and these variations are important in determining local membrane structure and function. The majority of membrane phospholipids are unsaturated, a condition which kinks their tails (increasing the space between them) and increases membrane fluidity. (See the illustration of phosphatidylcholine in Figure 2.16b, p. 46.) Glycolipids (gli ko-lip idz) are lipids with attached sugar groups. They are found only on the outer plasma membrane surface and account for about 5% of the total membrane lipid. Their sugar groups, like the phosphate-containing groups of phospholipids, make that end of the glycolipid molecule polar, whereas the fatty acid tails are nonpolar. Some 20% of membrane lipid is cholesterol. Like phospholipids, cholesterol has a polar region (its hydroxyl group) and a nonpolar region (its fused ring system). It wedges its platelike hydrocarbon rings between the phospholipid tails, stabilizing the membrane, while increasing the mobility of the phospholipids and the fluidity of the membrane. About 20% of the outer membrane surface contains lipid rafts, dynamic assemblies of saturated phospholipids (which pack together tightly) associated with unique lipids called sphingolipids and lots of cholesterol. These quiltlike patches are more stable and orderly and less fluid than the rest of the membrane, and they can include or exclude specific proteins to various extents. Because of these qualities, lipid rafts are assumed to be concentrating platforms for certain receptor molecules or for molecules needed for cell signaling. (Cell signaling will be discussed on pp ) Membrane Proteins Proteins make up about half of the plasma membrane by mass and are responsible for most of the specialized membrane functions. There are two distinct populations of membrane proteins, integral and peripheral (Figure.). Integral proteins are firmly inserted into the lipid bilayer. Some protrude from one membrane face only, but most are transmembrane proteins that span the entire width of the membrane and protrude on both sides. Whether transmembrane or not, all integral proteins have both hydrophobic and hydrophilic regions. This structural feature allows them to interact both with the nonpolar lipid tails buried in the membrane and with water inside and outside the cell. Although some are enzymes, most transmembrane proteins are involved in transport. Some cluster together to form channels, or pores, through which small, water-soluble molecules or ions can move, thus bypassing the lipid part of the membrane. Others act as carriers that bind to a substance and then move it through the membrane. Still others are receptors for hormones or other chemical messengers and relay messages to the cell interior (a process called signal transduction) (Figure.4a, b). Peripheral proteins (Figure.), in contrast, are not embedded in the lipid. Instead, they attach rather loosely only to integral proteins and are easily removed without disrupting the membrane. Peripheral proteins include a network of filaments that helps support the membrane from its cytoplasmic side (Figure.4c). Some peripheral proteins are enzymes. Others are motor proteins involved in mechanical functions, such as changing cell shape during cell division and muscle cell contraction. Still others link cells together. Some of the proteins float freely. Others, particularly the peripheral proteins, are restricted in their movements because they are tethered to intracellular structures that make up the cytoskeleton. Many of the proteins that abut the extracellular fluid are glycoproteins with branching sugar groups. The term glycocalyx (gli ko-kal iks; sugar covering ) is used to describe the fuzzy, sticky, carbohydrate-rich area at the cell surface. You can think of your cells as sugar-coated. The glycocalyx that clings to each cell s surface is enriched both by glycolipids and by glycoproteins secreted by the cell. Because every cell type has a different pattern of sugars in its glycocalyx, the glycocalyx provides highly specific biological markers by which approaching cells recognize each other (Figure.4f). For example, a sperm recognizes an ovum (egg cell) by the ovum s unique glycocalyx. Cells of the immune system identify a bacterium by binding to certain membrane glycoproteins in the bacterial glycocalyx.

5 Chapter Cells: The Living Units 65 Polar head of phospholipid molecule Cholesterol Extracellular fluid (watery environment) Glycolipid Glycoprotein Nonpolar tail of phospholipid molecule Carbohydrate of glycocalyx Bimolecular lipid layer containing proteins Outward-facing layer of phospholipids Inward-facing layer of phospholipids Cytoplasm (watery environment) Integral proteins Filament of cytoskeleton Peripheral proteins Figure. Structure of the plasma membrane according to the fluid mosaic model. The lipid bilayer forms the basic structure of the membrane. The associated proteins are involved in membrane functions such as membrane transport, catalysis, and cell-to-cell recognition.

6 66 UNIT 1 Organization of the Body (a) Transport A protein (left) that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. Some transport proteins (right) hydrolyze ATP as an energy source to actively pump substances across the membrane. HOMEOSTATIC IMBALANCE Definite changes in the glycocalyx occur in a cell that is becoming cancerous. In fact, a cancer cell s glycocalyx may change almost continuously, allowing it to keep ahead of immune system recognition mechanisms and avoid destruction. (Cancer is discussed on pp ) ATP CHECK YOUR UNDERSTANDING Signal (b) Receptors for signal transduction A membrane protein exposed to the outside of the cell may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external signal may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell.. What basic structure do all cellular membranes share? 4. Why do phospholipids, which form the greater part of cell membranes, organize into a bilayer tail-to-tail in a watery environment? 5. What is the importance of the glycocalyx in cell interactions? For answers, see Appendix G. Receptor (c) Attachment to the cytoskeleton and extracellular matrix (ECM) Elements of the cytoskeleton (cell s internal supports) and the extracellular matrix (fibers and other substances outside the cell) may be anchored to membrane proteins, which help maintain cell shape and fix the location of certain membrane proteins. Others play a role in cell movement or bind adjacent cells together. (d) Enzymatic activity Membrane Junctions Although certain cell types blood cells, sperm cells, and some phagocytic cells (which ingest and destroy bacteria and other substances) are footloose in the body, many other types, particularly epithelial cells, are knit into tight communities. Typically, three factors act to bind cells together: 1. Glycoproteins in the glycocalyx act as an adhesive. 2. Wavy contours of the membranes of adjacent cells fit together in a tongue-and-groove fashion.. Special membrane junctions are formed (Figure.5). Enzymes A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane act as a team that catalyzes sequential steps of a metabolic pathway as indicated (left to right) here. (e) Intercellular joining Membrane proteins of adjacent cells may be hooked together in various kinds of intercellular junctions. Some membrane proteins (CAMs) of this group provide temporary binding sites that guide cell migration and other cell-to-cell interactions. Because junctions are the most important factor securing cells together, let us look more closely at the various types. Tight Junctions In a tight junction, a series of integral protein molecules (including occludins and claudins) in the plasma membranes of adjacent cells fuse together, forming an impermeable junction that encircles the cell (Figure.5a). Tight junctions help prevent molecules from passing through the extracellular space between adjacent cells. For example, tight junctions between epithelial cells lining the digestive tract keep digestive enzymes and microorganisms in the intestine from seeping into the bloodstream. (Although called impermeable junctions, some tight junctions are somewhat leaky and may allow certain types of ions to pass.) CAMs Glycoprotein (f) Cell-cell recognition Some glycoproteins (proteins bonded to short chains of sugars) serve as identification tags that are specifically recognized by other cells. Figure.4 Membrane proteins perform many tasks. A single protein may perform some combination of these tasks. Desmosomes Desmosomes (des mo-sōmz; binding bodies ) are anchoring junctions mechanical couplings scattered like rivets along the sides of abutting cells that prevent their separation (Figure.5b). On the cytoplasmic face of each plasma membrane is a buttonlike thickening called a plaque.adjacent cells are held together by thin linker protein filaments (cadherins) that extend from the plaques and fit together like the teeth of a zipper in the intercellular space. Thicker keratin filaments (intermediate filaments, which form part of the cytoskeleton) extend from the cytoplasmic side of the plaque across the width of the cell to anchor to the plaque on the cell s opposite side. In this way, desmosomes not only bind neighboring cells together,

7 Chapter Cells: The Living Units 67 Plasma membranes of adjacent cells Microvilli Intercellular space Basement membrane Intercellular space Plaque Intercellular space Interlocking junctional proteins Intercellular space (a) Tight junctions: Impermeable junctions prevent molecules from passing through the intercellular space. Intermediate filament (keratin) Linker glycoproteins (cadherins) (b) Desmosomes: Anchoring junctions bind adjacent cells together and help form an internal tension-reducing network of fibers. Channel between cells (connexon) (c) Gap junctions: Communicating junctions allow ions and small molecules to pass from one cell to the next for intercellular communication. Figure.5 Cell junctions. An epithelial cell is shown joined to adjacent cells by three common types of cell junctions. (Note: Except for epithelia, it is unlikely that a single cell will have all three junction types.) but they also contribute to a continuous internal network of strong guy-wires. This arrangement distributes tension throughout a cellular sheet and reduces the chance of tearing when it is subjected to pulling forces. Desmosomes are abundant in tissues subjected to great mechanical stress, such as skin and heart muscle. Gap Junctions A gap junction,or nexus (nek sus; bond ), is a communicating junction between adjacent cells. At gap junctions the adjacent plasma membranes are very close, and the cells are connected by hollow cylinders called connexons (kŏnek sonz), composed of transmembrane proteins. The many different types of connexon proteins vary the selectivity of the gap junction channels. Ions, simple sugars, and other small molecules pass through these water-filled channels from one cell to the next (Figure.5c). Gap junctions are present in electrically excitable tissues, such as the heart and smooth muscle, where ion passage from cell to cell helps synchronize their electrical activity and contraction. CHECK YOUR UNDERSTANDING 6. What two types of membrane junctions would you expect to find between muscle cells of the heart? For answer, see Appendix G.

8 68 UNIT 1 Organization of the Body Figure.6 Diffusion. Molecules in solution move continuously and collide constantly with other molecules, causing them to move away from areas of their highest concentration and become evenly distributed. From left to right, molecules from a dye pellet diffuse into the surrounding water down their concentration gradient. The Plasma Membrane: Membrane Transport Relate plasma membrane structure to active and passive transport processes. Compare and contrast simple diffusion, facilitated diffusion, and osmosis relative to substances transported, direction, and mechanism. Our cells are bathed in an extracellular fluid called interstitial fluid (in ter-stish al) that is derived from the blood. Interstitial fluid is like a rich, nutritious soup. It contains thousands of ingredients, including amino acids, sugars, fatty acids, vitamins, regulatory substances such as hormones and neurotransmitters, salts, and waste products. To remain healthy, each cell must extract from this mix the exact amounts of the substances it needs at specific times. Although there is continuous traffic across the plasma membrane, it is a selectively, or differentially, permeable barrier, meaning that it allows some substances to pass while excluding others. It allows nutrients to enter the cell, but keeps many undesirable substances out. At the same time, it keeps valuable cell proteins and other substances in the cell, but allows wastes to exit. Substances move through the plasma membrane in essentially two ways passively or actively. In passive processes,substances cross the membrane without any energy input from the cell. In active processes, the cell provides the metabolic energy (ATP) needed to move substances across the membrane. The various transport processes that occur in cells are summarized in Table.1 on p. 72 and Table.2 on p. 80. Let s examine each of these types of membrane transport. HOMEOSTATIC IMBALANCE Selective permeability is a characteristic of healthy, intact cells. When a cell (or its plasma membrane) is severely damaged, the membrane becomes permeable to virtually everything, and substances flow into and out of the cell freely. This phenomenon is evident when someone has been severely burned. Precious fluids, proteins, and ions weep from the dead and damaged cells. Passive Processes The two main types of passive transport are diffusion (difu zhun) and filtration. Diffusion is an important means of passive membrane transport for every cell of the body. Because filtration generally occurs only across capillary walls, that topic is more properly covered in conjunction with capillary transport processes later in the book. Diffusion Diffusion is the tendency of molecules or ions to move from an area where they are in higher concentration to an area where they are in lower concentration, that is, down or along their concentration gradient. The constant random and high-speed motion of molecules and ions (a result of their intrinsic kinetic energy) results in collisions. With each collision, the particles ricochet off one another and change direction. The overall effect of this erratic movement is the scattering or dispersion of the particles throughout the environment (Figure.6). The greater the difference in concentration of the diffusing molecules and ions between the two areas, the more collisions occur and the faster the net diffusion of the particles. Because the driving force for diffusion is the kinetic energy of the molecules themselves, the speed of diffusion is influenced by molecular size (the smaller, the faster) and by temperature (the warmer, the faster). In a closed container, diffusion eventually produces a uniform mixture of molecules. In other words, the system reaches equilibrium, with molecules moving equally in all directions (no net movement). Diffusion is occurring all around us, but obvious examples of pure diffusion are almost impossible to see. The reason is that any diffusion process that occurs over an easily observable distance takes a long time, and is often accompanied by other processes (convection, for example) that affect the movement of molecules and ions. In fact, one should suspect any readily observable example of diffusion. Nonetheless, diffusion is immensely important in physiological systems and it occurs rapidly because the distances molecules are moving are very short, perhaps 1/1000 (or less) the thickness of this page! Examples include the movement of ions across cell membranes and the movement of neurotransmitters between two nerve cells. The plasma membrane is a physical barrier to free diffusion because of its hydrophobic core. However, a molecule will diffuse

9 Chapter Cells: The Living Units 69 Extracellular fluid Lipidsoluble solutes Lipid-insoluble solutes (such as sugars or amino acids) Small lipidinsoluble solutes Water molecules Lipid billayer Cytoplasm Aquaporin (a) Simple diffusion of fat-soluble molecules directly through the phospholipid bilayer (b) Carrier-mediated facilitated diffusion via a protein carrier specific for one chemical; binding of substrate causes shape change in transport protein (c) Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge (d) Osmosis, diffusion of a solvent such as water through a specific channel protein (aquaporin) or through the lipid bilayer Figure.7 Diffusion through the plasma membrane. through the membrane if the molecule is (1) lipid soluble, (2) small enough to pass through membrane channels, or () assisted by a carrier molecule. The unassisted diffusion of lipid-soluble or very small particles is called simple diffusion.a special name, osmosis, is given to the unassisted diffusion of a solvent (usually water) through a membrane. Assisted diffusion is known as facilitated diffusion. Simple Diffusion In simple diffusion, nonpolar and lipidsoluble substances diffuse directly through the lipid bilayer (Figure.7a). Such substances include oxygen, carbon dioxide, and fat-soluble vitamins. Because oxygen concentration is always higher in the blood than in tissue cells, oxygen continuously diffuses from the blood into the cells. Carbon dioxide, on the other hand, is in higher concentration within the cells, so it diffuses from tissue cells into the blood. Facilitated Diffusion Certain molecules, notably glucose and other sugars, some amino acids, and ions are transported passively even though they are unable to pass through the lipid bilayer. Instead they move through the membrane by a passive transport process called facilitated diffusion in which the transported substance either (1) binds to protein carriers in the membrane and is ferried across or (2) moves through waterfilled protein channels. Carriers are transmembrane integral proteins that show specificity for molecules of a certain polar substance or class of substances that are too large to pass through membrane channels, such as sugars and amino acids. The most popular model for the action of carriers indicates that changes in the shape of the carrier allow it to first envelop and then release the transported substance, shielding it en route from the nonpolar regions of the membrane. Essentially, the binding site is moved from one face of the membrane to the other by changes in the conformation of the carrier protein (Figure.7b and Table.1). Note that a substance transported by carrier-mediated facilitated diffusion, such as glucose, moves down its concentration gradient, just as in simple diffusion. Glucose is normally in higher concentrations in the blood than in the cells, where it is rapidly used for ATP synthesis. So, glucose transport within the body is typically unidirectional into the cells. However, carrier-mediated transport is limited by the number of protein carriers present. For example, when all the glucose carriers are engaged, they are said to be saturated, and glucose transport is occurring at its maximum rate. Channels are transmembrane proteins that serve to transport substances, usually ions or water, through aqueous channels from one side of the membrane to the other (Figure.7c and d). Binding or association sites exist within the channels, and the channels are selective due to pore size and the charges of the amino acids lining the channel. Some channels, the so-called leakage channels, are always open and simply allow ion or water fluxes according to concentration gradients. Others are gated and are controlled (opened or closed) by various chemical or electrical signals. Like carriers, many channels can be inhibited by certain molecules, show saturation, and tend to be specific. Substances moving through them also follow the concentration gradient (always moving down the gradient). When a substance crosses the membrane by simple diffusion, the rate of diffusion is not controllable because the lipid solubility of the membrane is not immediately changeable. By contrast, the rate of facilitated diffusion is controllable because the

10 70 UNIT 1 Organization of the Body (a) Membrane permeable to both solutes and water Solute and water molecules move down their concentration gradients in opposite directions. Fluid volume remains the same in both compartments. Left compartment: Solution with lower osmolarity Right compartment: Solution with greater osmolarity Both solutions have the same osmolarity: volume unchanged H 2 O Solute Membrane Solute molecules (sugar) (b) Membrane permeable to water, impermeable to solutes Solute molecules are prevented from moving but water moves by osmosis. Volume increases in the compartment with the higher osmolarity. Left compartment Right compartment Both solutions have identical osmolarity, but volume of the solution on the right is greater because only water is free to move H 2 O Membrane Solute molecules (sugar) Figure.8 Influence of membrane permeability on diffusion and osmosis. permeability of the membrane can be altered by regulating the activity or number of individual carriers or channels. Oxygen, water, glucose, and various ions are vitally important to cellular homeostasis. Their passive transport by diffusion (either simple or facilitated) represents a tremendous saving of cellular energy. Indeed, if these substances had to be transported actively, cell expenditures of ATP would increase exponentially! Osmosis The diffusion of a solvent, such as water, through a selectively permeable membrane is osmosis (oz-mo sis; osmos pushing). Even though water is highly polar, it passes via osmosis through the lipid bilayer (Figure.7d). This is surprising because you d expect water to be repelled by the hydrophobic lipid tails. Although still hypothetical, one explanation is that random movements of the membrane lipids open small gaps between their wiggling tails, allowing water to slip and slide its way through the membrane by moving from gap to gap. Water also moves freely and reversibly through water-specific channels constructed by transmembrane proteins called aquaporins (AQPs). Although aquaporins are believed to be present in all cell types, they are particularly abundant in red blood cells and in cells involved in water balance such as kidney tubule cells. Osmosis occurs whenever the water concentration differs on the two sides of a membrane. If distilled water is present on both sides of a selectively permeable membrane, no net osmosis occurs, even though water molecules move in both directions through the membrane. If the solute concentration on the two sides of

11 Chapter Cells: The Living Units 71 (a) Isotonic solutions Cells retain their normal size and shape in isotonic solutions (same solute/water concentration as inside cells; water moves in and out). (b) Hypertonic solutions Cells lose water by osmosis and shrink in a hypertonic solution (contains a higher concentration of solutes than are present inside the cells). (c) Hypotonic solutions Cells take on water by osmosis until they become bloated and burst (lyse) in a hypotonic solution (contains a lower concentration of solutes than are present in cells). Figure.9 The effect of solutions of varying tonicities on living red blood cells. the membrane differs, water concentration differs as well (as solute concentration increases, water concentration decreases). The extent to which water s concentration is decreased by solutes depends on the number, not the type, of solute particles, because one molecule or one ion of solute (theoretically) displaces one water molecule. The total concentration of all solute particles in a solution is referred to as the solution s osmolarity (oz mo-lar ĭ-te). When equal volumes of aqueous solutions of different osmolarity are separated by a membrane that is permeable to all molecules in the system, net diffusion of both solute and water occurs, each moving down its own concentration gradient. Eventually, equilibrium is reached when the water concentration on the left equals that on the right, and the solute concentration on both sides is the same (Figure.8a). If we consider the same system, but make the membrane impermeable to solute molecules, we see quite a different result (Figure.8b). Water quickly diffuses from the left to the right compartment and continues to do so until its concentration is the same on the two sides of the membrane. Notice that in this case equilibrium results from the movement of water alone (the solutes are prevented from moving). Notice also that the movement of water leads to dramatic changes in the volumes of the two compartments. The last example mimics osmosis across plasma membranes of living cells, with one major difference. In our examples, the volumes of the compartments are infinitely expandable and the effect of pressure exerted by the added weight of the higher fluid column is not considered. In living plant cells, which have rigid cell walls external to their plasma membranes, this is not the case. As water diffuses into the cell, the point is finally reached where the hydrostatic pressure (the back pressure exerted by water against the membrane) within the cell is equal to its osmotic pressure (the tendency of water to move into the cell by osmosis). At this point, there is no further (net) water entry. As a rule, the higher the amount of nondiffusible, or nonpenetrating, solutes in a cell, the higher the osmotic pressure and the greater the hydrostatic pressure that must be developed to resist further net water entry. However, such major changes in hydrostatic (and osmotic) pressures do not occur in living animal cells, which lack rigid cell walls. Osmotic imbalances cause animal cells to swell or shrink (due to net water gain or loss) until either the solute concentration is the same on both sides of the plasma membrane, or the membrane is stretched to its breaking point. Such changes in animal cells lead us to the important concept of tonicity (to-nis ĭ-te). As noted, many molecules, particularly intracellular proteins and selected ions, are prevented from diffusing through the plasma membrane. Consequently, any change in their concentration alters the water concentration on the two sides of the membrane and results in a net loss or gain of water by the cell. The ability of a solution to change the shape or tone of cells by altering their internal water volume is called tonicity (tono tension). Solutions with the same concentrations of nonpenetrating solutes as those found in cells (0.9% saline or 5% glucose) are isotonic ( the same tonicity ). Cells exposed to such solutions retain their normal shape, and exhibit no net loss or gain of water (Figure.9a). As you might expect, the body s extracellular fluids and most intravenous solutions (solutions infused into the body via a vein) are isotonic.

12 72 UNIT 1 Organization of the Body TABLE.1 Passive Membrane Transport Processes PROCESS ENERGY SOURCE DESCRIPTION EXAMPLES Diffusion Simple diffusion Kinetic energy Net movement of molecules from an area of their higher concentration to an area of their lower concentration, that is, along their concentration gradient Facilitated diffusion Kinetic energy Same as simple diffusion, but the diffusing substance is attached to a lipid-soluble membrane carrier protein or moves through a membrane channel Osmosis Kinetic energy Simple diffusion of water through a selectively permeable membrane Movement of fats, oxygen, carbon dioxide through the lipid portion of the membrane Movement of glucose and some ions into cells Movement of water into and out of cells directly through the lipid phase of the membrane or via membrane channels (aquaporins) Solutions with a higher concentration of nonpenetrating solutes than seen in the cell (for example, a strong saline solution) are hypertonic. Cells immersed in hypertonic solutions lose water and shrink, or crenate (kre nat) (Figure.9b). Solutions that are more dilute (contain a lower concentration of nonpenetrating solutes) than cells are called hypotonic.cells placed in a hypotonic solution plump up rapidly as water rushes into them (Figure.9c). Distilled water represents the most extreme example of hypotonicity. Because it contains no solutes, water continues to enter cells until they finally burst or lyse. Notice that osmolarity and tonicity are not the same thing. A solution s osmolarity is based solely on its total solute concentration. In contrast, its tonicity is based on how the solution affects cell volume, which depends on (1) solute concentration and (2) solute permeability of the plasma membrane. Osmolarity is expressed as osmoles per liter (osmol/l) where 1 osmol is equal to 1 mole of nonionizing molecules.* A 0.-osmol/L solution of NaCl is isotonic because sodium ions are usually prevented from diffusing through the plasma membrane. But if the cell is immersed in a 0.-osmol/L solution of a penetrating solute, the solute will enter the cell and water will follow. The cell will swell and burst, just as if it had been placed in pure water. Osmosis is extremely important in determining distribution of water in the various fluid-containing compartments of the body (in cells, in blood, and so on). In general, osmosis continues until osmotic and hydrostatic pressures acting at the membrane are equal. For example, water is forced out of capillary blood by the hydrostatic pressure of the blood against the capillary wall, but the presence in blood of solutes that are too large to cross the capillary membrane draws water back into the bloodstream. As a result, very little net loss of plasma fluid occurs. Simple diffusion and osmosis occurring directly through the plasma membrane are not selective processes. In those processes, whether a molecule can pass through the membrane *Osmolarity (Osm) is determined by multiplying molarity (moles per liter, or M) by the number of particles resulting from ionization. For example, since NaCl ionizes to Na Cl,a 1M solution of NaCl is a 2-Osm solution. For substances that do not ionize (e.g., glucose), molarity and osmolarity are the same. depends chiefly on its size or its solubility in lipid, not on its unique structure. Facilitated diffusion, on the other hand, is often highly selective. The carrier for glucose, for example, combines specifically with glucose, in much the same way an enzyme binds to its specific substrate and ion channels allow only selected ions to pass. HOMEOSTATIC IMBALANCE Hypertonic solutions are sometimes infused intravenously into the bloodstream of edematous patients (those swollen because water is retained in their tissues) to draw excess water out of the extracellular space and move it into the bloodstream so that it can be eliminated by the kidneys. Hypotonic solutions may be used (with care) to rehydrate the tissues of extremely dehydrated patients. In less extreme cases of dehydration, drinking hypotonic fluids (colas, apple juice, and sports drinks) usually does the trick. Table.1 summarizes passive membrane transport processes. CHECK YOUR UNDERSTANDING 7. What is the energy source for all types of diffusion? 8. What determines the direction of any diffusion process? 9. What are the two types of facilitated diffusion and how do they differ? For answers, see Appendix G. Active Processes Differentiate between primary and secondary active transport. Compare and contrast endocytosis and exocytosis in terms of function and direction. Compare and contrast pinocytosis, phagocytosis, and receptor-mediated endocytosis.

13 Whenever a cell uses the bond energy of ATP to move solutes across the membrane, the process is referred to as active. Substances moved actively across the plasma membrane are usually unable to pass in the necessary direction by passive transport processes. The substance may be too large to pass through the channels, incapable of dissolving in the lipid bilayer, or unable to move down its concentration gradient. There are two major means of active membrane transport: active transport and vesicular transport. Active Transport Active transport, like carrier-mediated facilitated diffusion, requires carrier proteins that combine specifically and reversibly with the transported substances. However, facilitated diffusion always follows concentration gradients because its driving force is kinetic energy. In contrast, the active transporters or solute pumps move solutes, most importantly ions (such as Na,K, and Ca 2 ), uphill against a concentration gradient. To do this work, cells must expend the energy of ATP. Active transport processes are distinguished according to their source of energy. In primary active transport, the energy to do work comes directly from hydrolysis of ATP.In secondary active transport, transport is driven indirectly by energy stored in ionic gradients created by operation of primary active transport pumps. Secondary active transport systems are all coupled systems; that is, they move more than one substance at a time. If the two transported substances are moved in the same direction, the system is a symport system (sym same). If the transported substances wave to each other as they cross the membrane in opposite directions, the system is an antiport system (anti opposite, against). Let s examine these processes more carefully. Primary Active Transport In primary active transport, hydrolysis of ATP results in the phosphorylation of the transport protein. This step causes the protein to change its shape in such a manner that it pumps the bound solute across the membrane. Primary active transport systems include calcium and hydrogen pumps, but the most investigated example of a primary active transport system is the operation of the sodiumpotassium pump, for which the carrier, or pump, is an enzyme called Na -K ATPase. In the body, the concentration of K inside the cell is some 10 times higher than that outside, and the reverse is true of Na. These ionic concentration differences are essential for excitable cells like muscle and nerve cells to function normally and for all body cells to maintain their normal fluid volume. Because Na and K leak slowly but continuously through leakage channels in the plasma membrane along their concentration gradient (and cross more rapidly in stimulated muscle and nerve cells), the Na -K Chapter Cells: The Living Units 7 pump operates more or less continuously as an antiporter. It simultaneously drives Na out of the cell against a steep concentration gradient and pumps K back in. The electrochemical gradients maintained by the Na -K pump underlie most primary and secondary active transport of nutrients and ions, and are crucial for cardiac and skeletal muscle and neuron function. The step-by-step operation of the Na -K pump is described in Focus on Primary Active Transport: The Na + -K + Pump (Figure.10) on p. 74. Make sure you understand this process thoroughly before moving on to the topic of secondary active transport. Secondary Active Transport A single ATP-powered pump, such as the Na -K pump, can indirectly drive the secondary active transport of several other solutes. By moving sodium across the plasma membrane against its concentration gradient, the pump stores energy (in the ion gradient). Then, just as water pumped uphill can do work as it flows back down (to turn a turbine or water wheel), a substance pumped across a membrane can do work as it leaks back, propelled downhill along its concentration gradient. In this way, as sodium moves back into the cell with the help of a carrier protein (facilitated diffusion), other substances are dragged along, or cotransported, by a common carrier protein (Figure.11). A carrier moving two substances in the same direction is a symport system. For example, some sugars, amino acids, and many ions are cotransported in this way into cells lining the small intestine. Both cotransported substances move passively because the energy for this type of transport is the concentration gradient of the ion (in this case Na ). Na has to be pumped back out into the lumen (cavity) of the intestine to maintain its diffusion gradient. Ion gradients can also be used to drive antiport systems such as those that help to regulate intracellular ph by using the sodium gradient to expel hydrogen ions. Regardless of whether the energy is provided directly (primary active transport) or indirectly (secondary active transport), each membrane pump or cotransporter transports only specific substances. For this reason, active transport systems provide a way for the cell to be very selective in cases where substances cannot pass by diffusion. (No pump no transport.) Vesicular Transport In vesicular transport, fluids containing large particles and macromolecules are transported across cellular membranes inside membranous sacs called vesicles. Vesicular transport processes that eject substances from the cell interior into the extracellular fluid are called exocytosis (ek so-si-to sis; out of the cell ). Those in which the cell ingests small patches of the plasma

14 Figure.10 FOCUS Primary Active Transport: The Na + -K + Pump Primary active transport is the process in which ions are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. The action of the Na + -K + pump is an important example of primary active transport. Extracellular fluid Na + Na + -K + pump ATP-binding site K + Na + bound Cytoplasm 1 Cytoplasmic Na + binds to pump protein. P K + released ATP ADP 6 K + is released from the pump protein and Na + sites are ready to bind Na + again. The cycle repeats. 2 Binding of Na + promotes phosphorylation of the protein by ATP. Na + released K + bound P P i K + 5 K + binding triggers release of the phosphate. Pump protein returns to its original conformation. Phosphorylation causes the protein to change shape, expelling Na + to the outside. P 4 Extracellular K + binds to pump protein. 74

15 Chapter Cells: The Living Units 75 Extracellular fluid Glucose Na + Na + Na+ K + Na + -K + pump Na + -glucose symport transporter loading glucose from ECF Na + Na + -glucose symport transporter releasing glucose into the cytoplasm ATP Na + Cytoplasm 1 The ATP-driven Na + -K + pump 2 As Na + diffuses back across the membrane stores energy by creating a steep concentration gradient for Na + entry into the cell. through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. (ECF = extracellular fluid) Figure.11 Secondary active transport. membrane and moves substances from the cell exterior to the cell interior are called endocytosis (en do-si-to sis; within the cell ). Vesicular transport is also used for combination processes such as transcytosis, moving substances into, across, and then out of the cell, and substance, or vesicular, trafficking, moving substances from one area (or organelle) in the cell to another. Like solute pumping, vesicular transport processes are energized by ATP (or in some cases another energy-rich compound, GTP guanosine triphosphate). Endocytosis, Transcytosis, and Vesicular Trafficking Virtually all forms of vesicular transport involve an assortment of protein-coated vesicles of three types and, with some exceptions, all are mediated by membrane receptors. Before we get specific about each type of coated vesicular transport, let s look at the general scheme of endocytosis. Protein-coated vesicles provide the main route for endocytosis and transcytosis of bulk solids, most macromolecules, and fluids. On occasion, these vesicles are also hijacked by pathogens seeking entry into a cell. Figure.12 shows the basic steps in endocytosis and transcytosis. 1 The substance to be taken into the cell by endocytosis is progressively enclosed by an infolding portion of the plasma membrane called a coated pit. The coating is most often the bristlelike clathrin (kla thrin; lattice clad ) protein coating found on the cytoplasmic face of the pit. The clathrin coat (clathrin and some accessory proteins) acts both in cargo selection and in deforming the membrane to produce the vesicle. 2 The vesicle detaches, and the coat proteins are recycled back to the plasma membrane. 4 The uncoated vesicle then typically fuses with a processing and sorting vesicle called an endosome. 5 Some membrane components and receptors of the fused vesicle may be recycled back to the plasma membrane in a transport vesicle. 6 The remaining contents of the vesicle may (a) combine with a lysosome (li sō-sōm), a specialized cell structure containing digestive enzymes, where the ingested substance is degraded or released (if iron or cholesterol), or (b) be transported completely across the cell and released by exocytosis on the opposite side (transcytosis). Transcytosis is common in the endothelial cells lining blood vessels because it provides a quick means to get substances from the blood to the interstitial fluid. Based on the nature and quantity of material taken up and the means of uptake, three types of endocytosis that use clathrin-coated vesicles are recognized: phagocytosis, pinocytosis, and receptor-mediated endocytosis. Phagocytosis (fag o-si-to sis; cell eating ) is the type of endocytosis in which the cell engulfs some relatively large or solid material, such as a clump of bacteria, cell debris, or inanimate particles (asbestos fibers or glass, for example) (Figure.1a). When a particle binds to receptors on the cell s surface, cytoplasmic extensions called pseudopods (soo do-pahdz; pseudo false, pod foot) form and flow around the particle and engulf it. The endocytotic vesicle formed in this way is called a phagosome (fag o-sōm; eaten body ). In most cases, the phagosome then fuses with a lysosome and its contents are digested. Any indigestible contents are ejected from the cell by exocytosis. In the human body, only macrophages and certain white blood cells are experts at phagocytosis. Commonly referred to as phagocytes, these cells help police and protect the body by ingesting and disposing of bacteria, other foreign substances, and dead tissue cells. The disposal of dying cells is crucial, because dead cell remnants trigger inflammation in the surrounding area or may stimulate an undesirable immune response. Most phagocytes move about by amoeboid motion (ah-me boyd; changing shape ); that is, the flowing of their cytoplasm into temporary pseudopods allows them to creep along.

16 76 UNIT 1 Organization of the Body 1 Coated pit ingests substance. Extracellular fluid Plasma membrane Protein coat (typically clathrin) 2 Protein-coated vesicle detaches. Cytoplasm Coat proteins detach and are recycled to plasma membrane. Transport vesicle Uncoated endocytic vesicle Endosome 4 Uncoated vesicle fuses with a 5 Transport vesicle sorting vesicle called an endosome. containing membrane components moves to the plasma membrane for recycling. Lysosome (a) 6 Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis). (b) Figure.12 Events of endocytosis mediated by protein-coated pits. Note the three possible fates for a vesicle and its contents, shown in 5 and 6. In pinocytosis ( cell drinking ), also called fluid-phase endocytosis, a bit of infolding plasma membrane (which begins as a clathrin-coated pit) surrounds a very small volume of extracellular fluid containing dissolved molecules (Figure.1b). This droplet enters the cell and fuses with an endosome. Unlike phagocytosis, pinocytosis is a routine activity of most cells, affording them a nonselective way of sampling the extracellular fluid. It is particularly important in cells that absorb nutrients, such as cells that line the intestines. As mentioned, bits of the plasma membrane are removed when the membranous sacs are internalized. However, these membranes are recycled back to the plasma membrane by exocytosis as described shortly, so the surface area of the plasma membrane remains remarkably constant. Receptor-mediated endocytosis is the main mechanism for the specific endocytosis and transcytosis of most macromolecules by body cells, and it is exquisitely selective (Figure.1c). It is also the mechanism that allows cells to concentrate material that is present only in very small amounts in the extracellular fluid. The receptors for this process are plasma membrane proteins that bind only certain substances. Both the receptors and attached molecules are internalized in a clathrin-coated pit and then dealt with in one of the ways discussed above. Substances taken up by receptor-mediated endocytosis include enzymes, insulin (and some other hormones), low-density lipoproteins (such as cholesterol attached to a transport protein), and iron. Unfortunately, flu viruses, diphtheria, and cholera toxins use this route to enter and attack our cells. Other coat proteins are also used for certain types of vesicular transport. Caveolae (ka ve-o le; little caves ), tubular or flaskshaped inpocketings of the plasma membrane seen in many cell types, are involved in a unique kind of receptor-mediated endocytosis called potosis. Like clathrin-coated pits, caveolae capture specific molecules (folic acid, tetanus toxin) from the extracellular fluid in coated vesicles and participate in some forms of transcytosis. However, caveolae are smaller than clathrin-coated

17 Chapter Cells: The Living Units 77 TABLE.2 Active Membrane Transport Processes PROCESS ENERGY SOURCE DESCRIPTION EXAMPLES Active Transport Primary active transport Secondary active transport ATP Ion concentration gradient maintained with ATP Transport of substances against a concentration (or electrochemical) gradient. Performed across the plasma membrane by a solute pump, directly using energy of ATP hydrolysis. Cotransport (coupled transport) of two solutes across the membrane. Energy is supplied indirectly by the ion gradient created by primary active transport. Symporters move the transported substances in the same direction; antiporters move transported substances in opposite directions across the membrane. Ions (Na, K, H, Ca 2, and others) Movement of polar or charged solutes, e.g., amino acids (into cell by symporters); Ca 2+, H + (out of cells via antiporters) Vesicular Transport Exocytosis ATP Secretion or ejection of substances from a cell. The substance is enclosed in a membranous vesicle, which fuses with the plasma membrane and ruptures, releasing the substance to the exterior. Endocytosis Via clathrin-coated vesicles ATP Phagocytosis ATP Cell eating : A large external particle (proteins, bacteria, dead cell debris) is surrounded by a seizing foot and becomes enclosed in a vesicle (phagosome). Pinocytosis (fluid-phase endocytosis) Receptormediated endocytosis Via caveolin-coated vesicles (caveolae) Intracellular vesicular trafficking Via coatomercoated vesicles ATP ATP ATP ATP Plasma membrane sinks beneath an external fluid droplet containing small solutes. Membrane edges fuse, forming a fluid-filled vesicle. Selective endocytosis and transcytosis. External substance binds to membrane receptors. Selective endocytosis (and transcytosis). External substance binds to membrane receptors (often associated with lipid rafts). Vesicles pinch off from organelles and travel to other organelles to deliver their cargo. Secretion of neurotransmitters, hormones, mucus, etc.; ejection of cell wastes In the human body, occurs primarily in protective phagocytes (some white blood cells and macrophages) Occurs in most cells; important for taking in dissolved solutes by absorptive cells of the kidney and intestine Means of intake of some hormones, cholesterol, iron, and most macromolecules Roles not fully known; proposed roles include cholesterol regulation and trafficking, and platforms for signal transduction Accounts for nearly all intracellular trafficking between certain organelles (endoplasmic reticulum and Golgi apparatus). Exceptions include vesicles budding from the trans face of the Golgi apparatus, which are clathrin-coated. vesicles. Additionally, their cage-like protein coat is thinner and composed of a different protein called caveolin. Caveolae are closely associated with lipid rafts that are platforms for G proteins, receptors for hormones (for example, insulin), and enzymes involved in cell regulation. These vesicles appear to provide sites for cell signaling and cross talk between signaling pathways. Their precise role in the cell is still being worked out. Vesicles coated with coatomer (COP1 and COP2) proteins are used in most types of intracellular vesicular trafficking, in which vesicles transport substances between organelles.

18 78 UNIT 1 Organization of the Body Phagosome (a) Phagocytosis The cell engulfs a large particle by forming projecting pseudopods ( false feet ) around it and enclosing it within a membrane sac called a phagosome. The phagosome is combined with a lysosome. Undigested contents remain in the vesicle (now called a residual body) or are ejected by exocytosis. Vesicle may or may not be proteincoated but has receptors capable of binding to microorganisms or solid particles. Extracellular fluid Secretory vesicle Plasma membrane SNARE (t-snare) Vesicle SNARE (v-snare) Molecule to be secreted Cytoplasm (a) The process of exocytosis 1 The membranebound vesicle migrates to the plasma membrane. (b) Pinocytosis The cell gulps drops of extracellular fluid containing solutes into tiny vesicles. No receptors are used, so the process is nonspecific. Most vesicles are protein-coated. Fused v- and t-snares 2 There, proteins at the vesicle surface (v-snares) bind with t-snares (plasma membrane proteins). Fusion pore formed Vesicle Receptor recycled to plasma membrane Vesicle (c) Receptor-mediated endocytosis Extracellular substances bind to specific receptor proteins in regions of coated pits, enabling the cell to ingest and concentrate specific substances (ligands) in protein-coated vesicles. Ligands may simply be released inside the cell, or combined with a lysosome to digest contents. Receptors are recycled to the plasma membrane in vesicles. The vesicle and plasma membrane fuse and a pore opens up. 4 Vesicle contents are released to the cell exterior. Figure.1 Comparison of three types of endocytosis. Exocytosis The process of exocytosis, typically stimulated by a cell-surface signal such as binding of a hormone to a membrane receptor or a change in membrane voltage, accounts for hormone secretion, neurotransmitter release, mucus secretion, and in some cases, ejection of wastes. The substance to be removed from the cell is first enclosed in a protein-coated membranous sac called a vesicle. In most cases, the vesicle migrates to the plasma membrane, fuses with it, and then ruptures, spilling the sac contents out of the cell (Figure.14). Exocytosis, like other cases in which vesicles are targeted to their destinations, involves a docking process in which transmembrane proteins on the vesicles, fancifully called v-snares (v for vesicle), recognize certain plasma membrane proteins, (b) Photomicrograph of a secretory vesicle releasing its contents by exocytosis (100,000 ) Figure.14 Exocytosis.

19 Chapter Cells: The Living Units 79 + Extracellular fluid K + + K + K + K + K + K + K+ Na + Cytoplasm Cl Na + Cl Potassium leakage channels A Na + K + K + K + K+ K+ K+ K + A + + Protein anion (unable to follow K + through the membrane) 1 K + diffuse down their steep concentration gradient (out of the cell) via leakage channels. Loss of K + results in a negative charge on the inner plasma membrane face. 2 K + also move into the cell because they are attracted to the negative charge established on the inner plasma membrane face. A negative membrane potential ( 90 mv) is established when the movement of K + out of the cell equals K + movement into the cell. At this point, the concentration gradient promoting K + exit exactly opposes the electrical gradient for K + entry. Figure.15 The key role of K + in generating the resting membrane potential. The resting membrane potential is largely determined by K + because the membrane is much more permeable to K + than Na + at rest. The active transport of sodium and potassium ions (in a ratio of :2) by the Na + -K + pump maintains these conditions. called t-snares (t for target), and bind with them. This binding causes the membranes to corkscrew together and fuse, rearranging the lipid monolayers without mixing them (Figure.14a). As described, membrane material added by exocytosis is removed by endocytosis the reverse process. Table.2 summarizes active membrane transport processes. CHECK YOUR UNDERSTANDING 10. What happens when the Na + -K + pump is phosphorylated? When K + binds to the pump protein? 11. As a cell grows, its plasma membrane expands. Does this membrane expansion involve endocytosis or exocytosis? 12. Phagocytic cells gather in the lungs, particularly in the lungs of smokers. What is the connection? 1. What vesicular transport process allows a cell to take in cholesterol from the extracellular fluid? For answers, see Appendix G. The Plasma Membrane: Generation of a Resting Membrane Potential Define membrane potential and explain how the resting membrane potential is established and maintained. As you re now aware, the selective permeability of the plasma membrane can lead to dramatic osmotic flows, but that is not its only consequence. An equally important result is the generation of a membrane potential, or voltage, across the membrane. A voltage is electrical potential energy resulting from the separation of oppositely charged particles. In cells, the oppositely charged particles are ions, and the barrier that keeps them apart is the plasma membrane. In their resting state, all body cells exhibit a resting membrane potential that typically ranges from 50 to 100 millivolts (mv), depending on cell type. For this reason, all cells are said to be polarized. The minus sign before the voltage indicates that the inside of the cell is negative compared to its outside. This voltage (or charge separation) exists only at the membrane.ifwe were to add up all the negative and positive charges in the cytoplasm, we would find that the cell interior is electrically neutral. Likewise, the positive and negative charges in the extracellular fluid balance each other exactly. So how does the resting membrane potential come about, and how is it maintained? The short answer is that diffusion causes ionic imbalances that polarize the membrane, and active transport processes maintain that membrane potential. First, let s look at how diffusion polarizes the membrane. Many kinds of ions are found both inside cells and in the extracellular fluid, but the resting membrane potential is determined mainly by the concentration gradient of potassium (K ) and by the differential permeability of the plasma membrane to K and other ions (Figure.15). Recall that K and protein anions predominate inside body cells, and the extracellular fluid contains relatively more Na, which is largely balanced by Cl. The unstimulated plasma membrane is somewhat permeable to K because of leakage channels, but impermeable to the protein anions. Consequently, K diffuses out of the cell along its concentration gradient but the protein anions are unable to follow,

20 80 UNIT 1 Organization of the Body and this loss of positive charges makes the membrane interior more negative (Figure.15). As more and more K leaves the cell, the negativity of the inner membrane face becomes great enough to attract K back toward and even into the cell. At this point ( 90 mv), potassium s concentration gradient is exactly balanced by the electrical gradient (membrane potential), and one K enters the cell as one leaves. In many cells, sodium (Na ) also contributes to the resting membrane potential. Sodium is strongly attracted to the cell interior by its concentration gradient, bringing the resting membrane potential to 70 mv. However, potassium still largely determines the resting membrane potential because the membrane is much more permeable to K than to Na. Even though the membrane is permeable to Cl, in most cells Cl does not contribute to the resting membrane potential, because its entry is resisted by the negative charge of the interior. We may be tempted to believe that massive flows of K ions are needed to generate the resting potential, but this is not the case. Surprisingly, the number of ions producing the membrane potential is so small that it does not change ion concentrations in any significant way. In a cell at rest, very few ions cross its plasma membrane. However, Na and K are not at equilibrium and there is some net movement of K out of the cell and of Na into the cell. Na is strongly pulled into the cell by both its concentration gradient and the interior negative charge. If only passive forces were at work, these ion concentrations would eventually become equal inside and outside the cell. Now let s look at how active transport processes maintain the membrane potential that diffusion has established, with the result that the cell exhibits a steady state. The rate of active transport is equal to, and depends on, the rate of Na diffusion into the cell. If more Na enters, more is pumped out. (This is like being in a leaky boat. The more water that comes in, the faster you bail!) The Na -K pump couples sodium and potassium transport and, on average, each turn of the pump ejects Na out of the cell and carries 2K back in (see Figure.10). Because the membrane is always 50 to 100 times more permeable to K, the ATP-dependent Na -K pump maintains both the membrane potential (the charge separation) and the osmotic balance. Indeed, if Na was not continuously removed from cells, in time so much would accumulate intracellularly that the osmotic gradient would draw water into the cells, causing them to burst. Now that we ve introduced the membrane potential, we can add a detail or two to our discussion of diffusion. Earlier we said that solutes diffuse down their concentration gradient. This is true for uncharged solutes, but only partially true for ions. The negatively and positively charged faces of the plasma membrane can help or hinder diffusion of ions driven by a concentration gradient. It is more correct to say that ions diffuse according to electrochemical gradients, thereby recognizing the effect of both electrical and concentration (chemical) forces. Consequently, although diffusion of K across the plasma membrane is aided by the membrane s greater permeability to it and by the ion s concentration gradient, its diffusion is resisted somewhat by the positive charge on the cell exterior. In contrast, Na is drawn into the cell by a steep electrochemical gradient, and the limiting factor is the membrane s relative impermeability to it. As we will describe in detail in later chapters, upsetting the resting membrane potential by transient opening of Na and K channels in the plasma membrane is a normal means of activating neurons and muscle cells. CHECK YOUR UNDERSTANDING 14. What event or process establishes the resting membrane potential? 15. Is the inside of the plasma membrane negative or positive relative to its outside in a polarized membrane? For answers, see Appendix G. The Plasma Membrane: Cell-Environment Interactions Describe the role of the glycocalyx when cells interact with their environment. List several roles of membrane receptors and that of voltage-sensitive membrane channel proteins. Cells are biological minifactories and, like other factories, they receive and send orders from and to the outside community. But how does a cell interact with its environment, and what activates it to carry out its homeostatic functions? Although cells sometimes interact directly with other cells, this is not always the case. In many cases cells respond to extracellular chemicals, such as hormones and neurotransmitters distributed in body fluids. Cells also interact with extracellular molecules that act as signposts to guide cell migration during development and repair. Whether cells interact directly or indirectly, however, the glycocalyx is always involved. The best understood of the participating glycocalyx molecules fall into two large families cell adhesion molecules and plasma membrane receptors (see Figure.4). Another group of membrane proteins, the voltage-sensitive channel proteins, are important in cells that respond to electrical signals. Roles of Cell Adhesion Molecules Thousands of cell adhesion molecules (CAMs) are found on almost every cell in the body. They play key roles in embryonic development and wound repair (situations where cell mobility is important) and in immunity. These sticky glycoproteins (cadherins and integrins) act as 1. The molecular Velcro that cells use to anchor themselves to molecules in the extracellular space and to each other (see desmosome discussion on pp ) 2. The arms that migrating cells use to haul themselves past one another. SOS signals sticking out from the blood vessel lining that rally protective white blood cells to a nearby infected or injured area